ENCePP Guide on Methodological Standards in Pharmacoepidemiology

5.2.1. Selection bias

Selection bias entails the
selective recruitment into the study of subjects that are not representative of
the exposure or outcome pattern in the source population. Examples of selection
bias are referral bias, self-selection bias, prevalence bias or protopathic bias
(Strom BL, Kimmel SE, Hennessy S. Pharmacoepidemiology, 5th Edition,
Wiley, 2012).

Protopathic bias

Protopathic bias arises when the
initiation of a drug (exposure) occurs in response to a symptom of the (at this
point undiagnosed) disease under study (outcome). For example, use of analgesics
in response to pain caused by an undiagnosed tumour might lead to the erroneous
conclusion that the analgesic caused the tumour. Protopathic bias thus reflects
a reversal of cause and effect (Bias:
Considerations for research practice. Am J Health Syst Pharm
2008;65:2159-68). This is particularly a problem in studies of drug-cancer
associations and other outcomes with long latencies. It may be handled by
including a time-lag, i.e. by disregarding all exposure during a specified
period of time before the index date.